Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer
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Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer. / Gong, Jian; Hutter, Carolyn M; Newcomb, Polly A; Ulrich, Cornelia M; Bien, Stephanie A; Campbell, Peter T; Baron, John A; Berndt, Sonja I; Bezieau, Stephane; Brenner, Hermann; Casey, Graham; Chan, Andrew T; Chang-Claude, Jenny; Du, Mengmeng; Duggan, David; Figueiredo, Jane C; Gallinger, Steven; Giovannucci, Edward L; Haile, Robert W; Harrison, Tabitha A; Hayes, Richard B; Hoffmeister, Michael; Hopper, John L; Hudson, Thomas J; Jeon, Jihyoun; Jenkins, Mark A; Kocarnik, Jonathan; Küry, Sébastien; Le Marchand, Loic; Lin, Yi-Ling; Lindor, Noralane M; Nishihara, Reiko; Ogino, Shuji; Potter, John D; Rudolph, Anja; Schoen, Robert E; Schrotz-King, Petra; Seminara, Daniela; Slattery, Martha L; Thibodeau, Stephen N; Thornquist, Mark; Toth, Reka; Wallace, Robert; White, Emily; Jiao, Shuo; Lemire, Mathieu; Hsu, Li; Peters, Ulrike; GECCO and CCFR.
in: PLOS GENET, Jahrgang 12, Nr. 10, 10.2016, S. e1006296.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer
AU - Gong, Jian
AU - Hutter, Carolyn M
AU - Newcomb, Polly A
AU - Ulrich, Cornelia M
AU - Bien, Stephanie A
AU - Campbell, Peter T
AU - Baron, John A
AU - Berndt, Sonja I
AU - Bezieau, Stephane
AU - Brenner, Hermann
AU - Casey, Graham
AU - Chan, Andrew T
AU - Chang-Claude, Jenny
AU - Du, Mengmeng
AU - Duggan, David
AU - Figueiredo, Jane C
AU - Gallinger, Steven
AU - Giovannucci, Edward L
AU - Haile, Robert W
AU - Harrison, Tabitha A
AU - Hayes, Richard B
AU - Hoffmeister, Michael
AU - Hopper, John L
AU - Hudson, Thomas J
AU - Jeon, Jihyoun
AU - Jenkins, Mark A
AU - Kocarnik, Jonathan
AU - Küry, Sébastien
AU - Le Marchand, Loic
AU - Lin, Yi-Ling
AU - Lindor, Noralane M
AU - Nishihara, Reiko
AU - Ogino, Shuji
AU - Potter, John D
AU - Rudolph, Anja
AU - Schoen, Robert E
AU - Schrotz-King, Petra
AU - Seminara, Daniela
AU - Slattery, Martha L
AU - Thibodeau, Stephen N
AU - Thornquist, Mark
AU - Toth, Reka
AU - Wallace, Robert
AU - White, Emily
AU - Jiao, Shuo
AU - Lemire, Mathieu
AU - Hsu, Li
AU - Peters, Ulrike
AU - GECCO and CCFR
PY - 2016/10
Y1 - 2016/10
N2 - Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4) and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.
AB - Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4) and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.
KW - Aged
KW - Alcohol Drinking
KW - Colorectal Neoplasms
KW - Female
KW - Gene-Environment Interaction
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Male
KW - Membrane Transport Proteins
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Smoking
KW - Tumor Suppressor Proteins
KW - Journal Article
U2 - 10.1371/journal.pgen.1006296
DO - 10.1371/journal.pgen.1006296
M3 - SCORING: Journal article
C2 - 27723779
VL - 12
SP - e1006296
JO - PLOS GENET
JF - PLOS GENET
SN - 1553-7404
IS - 10
ER -